rs374147064
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_001267550.2(TTN):c.88733G>A(p.Arg29578His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R29578R) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.88733G>A | p.Arg29578His | missense_variant | 332/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2043+12253C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.88733G>A | p.Arg29578His | missense_variant | 332/363 | 5 | NM_001267550.2 | P1 | |
ENST00000624360.1 | n.54C>T | non_coding_transcript_exon_variant | 1/1 | ||||||
TTN-AS1 | ENST00000659121.1 | n.416+30978C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000309 AC: 47AN: 152130Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000113 AC: 28AN: 248706Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 134908
GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461622Hom.: 0 Cov.: 32 AF XY: 0.0000468 AC XY: 34AN XY: 727096
GnomAD4 genome ? AF: 0.000302 AC: 46AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23AN XY: 74444
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:2
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 26, 2021 | - - |
Likely benign, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 08, 2022 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Primary dilated cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | research | Genetics and Genomics Program, Sidra Medicine | - | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 18, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at